RU2494095C2 - Модифицированные миметики лизина - Google Patents
Модифицированные миметики лизина Download PDFInfo
- Publication number
- RU2494095C2 RU2494095C2 RU2008126246/04A RU2008126246A RU2494095C2 RU 2494095 C2 RU2494095 C2 RU 2494095C2 RU 2008126246/04 A RU2008126246/04 A RU 2008126246/04A RU 2008126246 A RU2008126246 A RU 2008126246A RU 2494095 C2 RU2494095 C2 RU 2494095C2
- Authority
- RU
- Russia
- Prior art keywords
- benzamido
- carboxamide
- pyrrolidine
- carboxylic acid
- aminoacetyl
- Prior art date
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- 150000001875 compounds Chemical class 0.000 claims abstract 19
- 150000003839 salts Chemical class 0.000 claims abstract 15
- 208000024172 Cardiovascular disease Diseases 0.000 claims abstract 5
- 229910052736 halogen Inorganic materials 0.000 claims abstract 5
- 125000005843 halogen group Chemical group 0.000 claims abstract 5
- 230000003288 anthiarrhythmic effect Effects 0.000 claims abstract 2
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims abstract 2
- 229910052794 bromium Inorganic materials 0.000 claims abstract 2
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims abstract 2
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims abstract 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims abstract 2
- 239000003814 drug Substances 0.000 claims abstract 2
- 229910052740 iodine Inorganic materials 0.000 claims abstract 2
- 125000000217 alkyl group Chemical group 0.000 claims 9
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Chemical compound OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 claims 6
- 229910052799 carbon Inorganic materials 0.000 claims 5
- -1 2-aminoacetyl Chemical group 0.000 claims 4
- 230000001575 pathological effect Effects 0.000 claims 4
- BIZKIHUJGMSVFD-UHFFFAOYSA-N 1-(2-aminoacetyl)-4-benzamidopyrrolidine-2-carboxylic acid Chemical compound C1C(C(O)=O)N(C(=O)CN)CC1NC(=O)C1=CC=CC=C1 BIZKIHUJGMSVFD-UHFFFAOYSA-N 0.000 claims 2
- 206010003658 Atrial Fibrillation Diseases 0.000 claims 2
- 206010003662 Atrial flutter Diseases 0.000 claims 2
- BIZKIHUJGMSVFD-MNOVXSKESA-N danegaptide Chemical compound C1[C@@H](C(O)=O)N(C(=O)CN)C[C@@H]1NC(=O)C1=CC=CC=C1 BIZKIHUJGMSVFD-MNOVXSKESA-N 0.000 claims 2
- 238000000034 method Methods 0.000 claims 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 2
- 208000003663 ventricular fibrillation Diseases 0.000 claims 2
- 206010047302 ventricular tachycardia Diseases 0.000 claims 2
- IUYNNZGFAZFAQV-OLZOCXBDSA-N (2s,4r)-1-(2-acetamidoacetyl)-4-benzamidopyrrolidine-2-carboxylic acid Chemical compound C1[C@@H](C(O)=O)N(C(=O)CNC(=O)C)C[C@@H]1NC(=O)C1=CC=CC=C1 IUYNNZGFAZFAQV-OLZOCXBDSA-N 0.000 claims 1
- DWBJILOIAXQNOL-KOLCDFICSA-N (2s,4r)-1-(2-aminoacetyl)-4-[(4-hydroxybenzoyl)amino]pyrrolidine-2-carboxylic acid Chemical compound C1[C@@H](C(O)=O)N(C(=O)CN)C[C@@H]1NC(=O)C1=CC=C(O)C=C1 DWBJILOIAXQNOL-KOLCDFICSA-N 0.000 claims 1
- JDVMUTUTRUIQMU-PWSUYJOCSA-N (2s,4r)-1-(2-aminoacetyl)-4-[(4-methoxybenzoyl)amino]pyrrolidine-2-carboxylic acid Chemical compound C1=CC(OC)=CC=C1C(=O)N[C@H]1CN(C(=O)CN)[C@H](C(O)=O)C1 JDVMUTUTRUIQMU-PWSUYJOCSA-N 0.000 claims 1
- XMMUSAHYRGRXKP-NEPJUHHUSA-N (2s,4r)-1-(2-aminoacetyl)-4-[(4-methylbenzoyl)amino]pyrrolidine-2-carboxylic acid Chemical compound C1=CC(C)=CC=C1C(=O)N[C@H]1CN(C(=O)CN)[C@H](C(O)=O)C1 XMMUSAHYRGRXKP-NEPJUHHUSA-N 0.000 claims 1
- JKKQXROZVXIGNK-KOLCDFICSA-N (2s,4r)-1-(2-aminoacetyl)-4-[(4-nitrobenzoyl)amino]pyrrolidine-2-carboxylic acid Chemical compound C1[C@@H](C(O)=O)N(C(=O)CN)C[C@@H]1NC(=O)C1=CC=C([N+]([O-])=O)C=C1 JKKQXROZVXIGNK-KOLCDFICSA-N 0.000 claims 1
- AFKYIJMERVTDOP-CABCVRRESA-N (2s,4r)-1-(2-aminoacetyl)-4-benzamido-n-(2-methylpropyl)pyrrolidine-2-carboxamide Chemical compound C1N(C(=O)CN)[C@H](C(=O)NCC(C)C)C[C@H]1NC(=O)C1=CC=CC=C1 AFKYIJMERVTDOP-CABCVRRESA-N 0.000 claims 1
- PAJLKUPZKGQFHA-CABCVRRESA-N (2s,4r)-1-(2-aminoacetyl)-4-benzamido-n-cyclobutylpyrrolidine-2-carboxamide Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)CN)NC(=O)C=1C=CC=CC=1)NC1CCC1 PAJLKUPZKGQFHA-CABCVRRESA-N 0.000 claims 1
- CBVDJXWFMABTBY-OLZOCXBDSA-N (2s,4r)-1-(2-aminoacetyl)-4-benzamido-n-ethylpyrrolidine-2-carboxamide Chemical compound C1N(C(=O)CN)[C@H](C(=O)NCC)C[C@H]1NC(=O)C1=CC=CC=C1 CBVDJXWFMABTBY-OLZOCXBDSA-N 0.000 claims 1
- WQWSVVLBWHFEFE-NEPJUHHUSA-N (2s,4r)-1-(2-aminoacetyl)-4-benzamido-n-methylpyrrolidine-2-carboxamide Chemical compound C1N(C(=O)CN)[C@H](C(=O)NC)C[C@H]1NC(=O)C1=CC=CC=C1 WQWSVVLBWHFEFE-NEPJUHHUSA-N 0.000 claims 1
- GNBLZICAKJXKIV-KGLIPLIRSA-N (2s,4r)-1-(2-aminoacetyl)-4-benzamido-n-propan-2-ylpyrrolidine-2-carboxamide Chemical compound C1N(C(=O)CN)[C@H](C(=O)NC(C)C)C[C@H]1NC(=O)C1=CC=CC=C1 GNBLZICAKJXKIV-KGLIPLIRSA-N 0.000 claims 1
- CHINWZHDRJXXNZ-KGLIPLIRSA-N (2s,4r)-1-(2-aminoacetyl)-4-benzamido-n-tert-butylpyrrolidine-2-carboxamide Chemical compound C1N(C(=O)CN)[C@H](C(=O)NC(C)(C)C)C[C@H]1NC(=O)C1=CC=CC=C1 CHINWZHDRJXXNZ-KGLIPLIRSA-N 0.000 claims 1
- HTXAMMYKSMZQMY-MNOVXSKESA-N (2s,4r)-1-(2-aminoacetyl)-4-benzamidopyrrolidine-2-carboxamide Chemical compound C1[C@@H](C(N)=O)N(C(=O)CN)C[C@@H]1NC(=O)C1=CC=CC=C1 HTXAMMYKSMZQMY-MNOVXSKESA-N 0.000 claims 1
- XMYARXHHOGTBQV-NEPJUHHUSA-N (2s,4r)-4-benzamido-1-(2-formamidoacetyl)pyrrolidine-2-carboxylic acid Chemical compound C1N(C(=O)CNC=O)[C@H](C(=O)O)C[C@H]1NC(=O)C1=CC=CC=C1 XMYARXHHOGTBQV-NEPJUHHUSA-N 0.000 claims 1
- UVVZGPLJJCGVRQ-MNOVXSKESA-N (2s,4r)-4-benzamido-1-[2-[(2,2,2-trifluoroacetyl)amino]acetyl]pyrrolidine-2-carboxylic acid Chemical compound C1N(C(=O)CNC(=O)C(F)(F)F)[C@H](C(=O)O)C[C@H]1NC(=O)C1=CC=CC=C1 UVVZGPLJJCGVRQ-MNOVXSKESA-N 0.000 claims 1
- IUYNNZGFAZFAQV-UHFFFAOYSA-N 1-(2-acetamidoacetyl)-4-benzamidopyrrolidine-2-carboxylic acid Chemical compound C1C(C(O)=O)N(C(=O)CNC(=O)C)CC1NC(=O)C1=CC=CC=C1 IUYNNZGFAZFAQV-UHFFFAOYSA-N 0.000 claims 1
- DWBJILOIAXQNOL-UHFFFAOYSA-N 1-(2-aminoacetyl)-4-[(4-hydroxybenzoyl)amino]pyrrolidine-2-carboxylic acid Chemical compound C1C(C(O)=O)N(C(=O)CN)CC1NC(=O)C1=CC=C(O)C=C1 DWBJILOIAXQNOL-UHFFFAOYSA-N 0.000 claims 1
- JDVMUTUTRUIQMU-UHFFFAOYSA-N 1-(2-aminoacetyl)-4-[(4-methoxybenzoyl)amino]pyrrolidine-2-carboxylic acid Chemical compound C1=CC(OC)=CC=C1C(=O)NC1CN(C(=O)CN)C(C(O)=O)C1 JDVMUTUTRUIQMU-UHFFFAOYSA-N 0.000 claims 1
- XMMUSAHYRGRXKP-UHFFFAOYSA-N 1-(2-aminoacetyl)-4-[(4-methylbenzoyl)amino]pyrrolidine-2-carboxylic acid Chemical compound C1=CC(C)=CC=C1C(=O)NC1CN(C(=O)CN)C(C(O)=O)C1 XMMUSAHYRGRXKP-UHFFFAOYSA-N 0.000 claims 1
- JKKQXROZVXIGNK-UHFFFAOYSA-N 1-(2-aminoacetyl)-4-[(4-nitrobenzoyl)amino]pyrrolidine-2-carboxylic acid Chemical compound C1C(C(O)=O)N(C(=O)CN)CC1NC(=O)C1=CC=C([N+]([O-])=O)C=C1 JKKQXROZVXIGNK-UHFFFAOYSA-N 0.000 claims 1
- AFKYIJMERVTDOP-UHFFFAOYSA-N 1-(2-aminoacetyl)-4-benzamido-n-(2-methylpropyl)pyrrolidine-2-carboxamide Chemical compound C1N(C(=O)CN)C(C(=O)NCC(C)C)CC1NC(=O)C1=CC=CC=C1 AFKYIJMERVTDOP-UHFFFAOYSA-N 0.000 claims 1
- PAJLKUPZKGQFHA-UHFFFAOYSA-N 1-(2-aminoacetyl)-4-benzamido-n-cyclobutylpyrrolidine-2-carboxamide Chemical compound NCC(=O)N1CC(NC(=O)C=2C=CC=CC=2)CC1C(=O)NC1CCC1 PAJLKUPZKGQFHA-UHFFFAOYSA-N 0.000 claims 1
- JNDRSZHDKARQHT-UHFFFAOYSA-N 1-(2-aminoacetyl)-4-benzamido-n-cyclopentylpyrrolidine-2-carboxamide Chemical compound NCC(=O)N1CC(NC(=O)C=2C=CC=CC=2)CC1C(=O)NC1CCCC1 JNDRSZHDKARQHT-UHFFFAOYSA-N 0.000 claims 1
- CBVDJXWFMABTBY-UHFFFAOYSA-N 1-(2-aminoacetyl)-4-benzamido-n-ethylpyrrolidine-2-carboxamide Chemical compound C1N(C(=O)CN)C(C(=O)NCC)CC1NC(=O)C1=CC=CC=C1 CBVDJXWFMABTBY-UHFFFAOYSA-N 0.000 claims 1
- WQWSVVLBWHFEFE-UHFFFAOYSA-N 1-(2-aminoacetyl)-4-benzamido-n-methylpyrrolidine-2-carboxamide Chemical compound C1N(C(=O)CN)C(C(=O)NC)CC1NC(=O)C1=CC=CC=C1 WQWSVVLBWHFEFE-UHFFFAOYSA-N 0.000 claims 1
- GNBLZICAKJXKIV-UHFFFAOYSA-N 1-(2-aminoacetyl)-4-benzamido-n-propan-2-ylpyrrolidine-2-carboxamide Chemical compound C1N(C(=O)CN)C(C(=O)NC(C)C)CC1NC(=O)C1=CC=CC=C1 GNBLZICAKJXKIV-UHFFFAOYSA-N 0.000 claims 1
- CHINWZHDRJXXNZ-UHFFFAOYSA-N 1-(2-aminoacetyl)-4-benzamido-n-tert-butylpyrrolidine-2-carboxamide Chemical compound C1N(C(=O)CN)C(C(=O)NC(C)(C)C)CC1NC(=O)C1=CC=CC=C1 CHINWZHDRJXXNZ-UHFFFAOYSA-N 0.000 claims 1
- HTXAMMYKSMZQMY-UHFFFAOYSA-N 1-(2-aminoacetyl)-4-benzamidopyrrolidine-2-carboxamide Chemical compound C1C(C(N)=O)N(C(=O)CN)CC1NC(=O)C1=CC=CC=C1 HTXAMMYKSMZQMY-UHFFFAOYSA-N 0.000 claims 1
- XMYARXHHOGTBQV-UHFFFAOYSA-N 4-benzamido-1-(2-formamidoacetyl)pyrrolidine-2-carboxylic acid Chemical compound C1N(C(=O)CNC=O)C(C(=O)O)CC1NC(=O)C1=CC=CC=C1 XMYARXHHOGTBQV-UHFFFAOYSA-N 0.000 claims 1
- UVVZGPLJJCGVRQ-UHFFFAOYSA-N 4-benzamido-1-[2-[(2,2,2-trifluoroacetyl)amino]acetyl]pyrrolidine-2-carboxylic acid Chemical compound C1N(C(=O)CNC(=O)C(F)(F)F)C(C(=O)O)CC1NC(=O)C1=CC=CC=C1 UVVZGPLJJCGVRQ-UHFFFAOYSA-N 0.000 claims 1
- KPGGKSWVSBIMSD-UHFFFAOYSA-N 4-benzamido-1-[2-[(2-methylpropan-2-yl)oxycarbonylamino]acetyl]pyrrolidine-2-carboxylic acid Chemical compound C1C(C(O)=O)N(C(=O)CNC(=O)OC(C)(C)C)CC1NC(=O)C1=CC=CC=C1 KPGGKSWVSBIMSD-UHFFFAOYSA-N 0.000 claims 1
- 229910052801 chlorine Inorganic materials 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 230000001747 exhibiting effect Effects 0.000 claims 1
- 229910052731 fluorine Inorganic materials 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- UUEVFMOUBSLVJW-UHFFFAOYSA-N oxo-[[1-[2-[2-[2-[4-(oxoazaniumylmethylidene)pyridin-1-yl]ethoxy]ethoxy]ethyl]pyridin-4-ylidene]methyl]azanium;dibromide Chemical group [Br-].[Br-].C1=CC(=C[NH+]=O)C=CN1CCOCCOCCN1C=CC(=C[NH+]=O)C=C1 UUEVFMOUBSLVJW-UHFFFAOYSA-N 0.000 claims 1
- 238000011321 prophylaxis Methods 0.000 claims 1
- VLJNHYLEOZPXFW-UHFFFAOYSA-N pyrrolidine-2-carboxamide Chemical compound NC(=O)C1CCCN1 VLJNHYLEOZPXFW-UHFFFAOYSA-N 0.000 claims 1
- 125000001424 substituent group Chemical group 0.000 claims 1
- 238000011282 treatment Methods 0.000 claims 1
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 abstract 6
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 abstract 1
- 230000000694 effects Effects 0.000 abstract 1
- 239000000126 substance Substances 0.000 abstract 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 abstract 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 abstract 1
- 0 CN(*)C(CC1C(*)=O)CN1C(C(*)I)=O Chemical compound CN(*)C(CC1C(*)=O)CN1C(C(*)I)=O 0.000 description 1
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- C07—ORGANIC CHEMISTRY
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- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/16—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
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- C07C233/64—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings
- C07C233/81—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups
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| UA120353C2 (uk) * | 2013-09-10 | 2019-11-25 | Хромоселл Корпорейшн | Модулятори натрієвого каналу для лікування болю і діабету |
| US10010541B2 (en) | 2014-01-30 | 2018-07-03 | The Board Of Trustees Of The Leland Stanford Junior University | Modulation of tissue transglutaminase activation in disease |
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| JP7210540B2 (ja) | 2017-08-04 | 2023-01-23 | 武田薬品工業株式会社 | 血漿カリクレインの阻害剤およびその使用 |
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| MX2020003190A (es) | 2017-09-22 | 2020-11-11 | Kymera Therapeutics Inc | Degradadores de proteinas y usos de los mismos. |
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| US11292792B2 (en) | 2018-07-06 | 2022-04-05 | Kymera Therapeutics, Inc. | Tricyclic CRBN ligands and uses thereof |
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| US12187744B2 (en) | 2021-10-29 | 2025-01-07 | Kymera Therapeutics, Inc. | IRAK4 degraders and synthesis thereof |
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- 2006-12-21 RU RU2008126246/04A patent/RU2494095C2/ru active
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